Overweight, Obesity in 'Early Old Age' Tied to Cortical Thinning

Pauline Anderson

July 24, 2019

Greater body mass index (BMI) and waist circumference (WC) are associated with cortical thinning in the brain, especially in early old age, new research shows.

Michelle Caunca, PhD

The new results are important as poor brain health in aging populations is "an urgent public health concern," especially when "there's a lack of curative therapies for dementia," lead author Michelle R. Caunca, PhD, Medical Scientist Training Program, University of Miami Miller School of Medicine in Florida, told Medscape Medical News.

"Managing obesity, especially in those under age 65 years, may help preserve brain health in later life," Caunca said.

The study was published online today in Neurology.

Signs of "Brain Aging"

Although obesity, particularly in midlife, has been previously linked to increased risk for dementia, the causal mechanisms have been unclear and most data come from primarily non-Hispanic white subjects.

The investigators examined data from the Northern Manhattan MRI Sub-Study (NOMAS), an ongoing longitudinal cohort study of diverse, stroke-free, community-based adults over age 50.

The study included 1289 subjects with an average age of 64 years. The sample was 60% women and 66% Hispanic/Latino.

The investigators examined obesity and overweight. Overweight was defined as a BMI of 25 to 25.9 and obesity as a BMI of 30 or higher. They also looked at WC and waist-to-hip ratio (WHR).

Subjects underwent brain MRI an average of 6 years after the study began. Researchers examined a number of MRI markers of "brain aging," or signals of shrinkage and weakening of both gray matter and white matter structure.

These markers included total cerebral volume (TCV), which includes gray and white matter, total intracranial volume (TIV), white matter hyperintensity volume (WMHV), and subclinical brain infarct (SBI). Data on cortical thickness, a crude measure of the robustness of the outer "layer" of neurons that captures only gray matter, were available for a subsample of 947 subjects.

Researchers modeled TCV, WMHV, and cortical thickness using unadjusted and multivariable linear regression models, and modeled SBI using unadjusted and multivariable logistic regression models.

They converted TCV and cortical thickness into z score units, and presented beta (β) estimates (or odds ratios [ORs]) and 95% confidence intervals (CIs).

The analysis showed that compared with the reference weight, obesity was associated with smaller cortical thickness (BMI β −0.089; 95% CI, −0.153 to −0.025; P < .05), after adjusting for demographic and vascular risk factors. Greater waist circumference was also associated with a thinner cortex (WC β −0.103, 95% CI, −0.169 to −0.037; P < .05) in the fully adjusted model.

The associations were particularly evident for those younger than 65 years. This, said Caunca, is in line with the growing literature supporting the notion that obesity in midlife is associated with greater risk of dementia later in life.

Associations between cortical thickness and other obesity measures did not reach statistical significance in adjusted models.

Greater BMI and greater WC were both significantly associated with smaller TCV after adjusting for demographic risk factors. The strength of these associations remained consistent after adjusting for vascular risk factors, but the associations were no longer statistically significant.

"Since we observed stronger associations with cortical thickness, our findings suggest that obesity might be more related to gray matter than white matter. This suggests that obesity might increase risk of dementia by damaging gray matter," said Caunca.

Racial Differences

The associations between BMI and MRI brain markers varied in strength by race/ethnicity and sex. For example, associations between greater BMI and smaller TCV were especially notable for both Hispanics/Latinos and non-Hispanic blacks, although results did not reach statistical significance for the latter group.

"This may reflect differential risks for obesity in these minority groups compared to non-Hispanic whites," noted Caunca.

It's important to study brain aging in a racially/ethnically diverse sample because dementia risk differs between such groups, she said.

In men, greater central obesity, defined by waist circumference, was related to greater odds of SBI (OR, 1.998; 95% CI, 1.161 - 3.437), but this was not the case for women.

Caunca emphasized that associations uncovered by the study should be confirmed in larger studies with greater power to detect differences across groups.

The new findings lend some support to the American Heart Association/American Stroke Association proposed guidelines for optimal brain health that include a recommendation to keep BMI under 25.

Thoughtful Analysis

Commenting on the study for Medscape Medical News, David Knopman, MD, a clinical neurologist at the Mayo Clinic in Rochester, Minnesota, who is involved in research involving late-life cognitive disorders, called the study "a thoughtful analysis."

The finding of an association between measures of obesity and thinner cerebral cortices is "key," said Knopman. "Cortical thickness is an important measure of brain health, and its integrity is essential for preserved cognitive function later in life."

Although the mechanism by which obesity leads to cortical thinning is unclear, the association is "relevant for current public health concerns because of the obesity epidemic," said Knopman.  

"Fifteen years from now, obese middle-aged adults are going to be at greater risk for dementia."

Knopman found it "interesting" that the researchers found no association with obesity measures and WMHVs; white matter hyperintensities and cortical thickness are measures of cerebrovascular health.

"To the extent that obesity would be expected to operate through cerebrovascular mechanisms, the results show that the processes are more complicated," he said.

Knopman noted that the results "should not be construed as having any direct relationship to Alzheimer's disease, in the sense that Alzheimer's disease refers to neuritic plaques and neurofibrillary tangles."

Caunca and Knopman have disclosed no relevant financial relationships. The study was funded by the National Institute of Neurological Disorders and Stroke (NINDS) and the Evelyn F. McKnight Brain Institute.

Neurology. Published online July 24, 2019. Abstract

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